Rapid Induction of Dendritic Spine Morphogenesis by trans-Synaptic EphrinB-EphB Receptor Activation of the Rho-GEF Kalirin

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The morphogenesis of dendritic spines, the major sites of excitatory synaptic transmission in the brain, is important in synaptic development and plasticity. We have identified an ephrinB-EphB receptor trans-synaptic signaling pathway which regulates the morphogenesis and maturation of dendritic spines in hippocampal neurons. Activation of the EphB receptor induces translocation of the Rho-GEF kalirin to synapses and activation of Rac1 and its effector PAK. Overexpression of dominant-negative EphB receptor, catalytically inactive kalirin, or dominant-negative Rac1, or inhibition of PAK eliminates ephrin-induced spine development. This novel signal transduction pathway may be critical for the regulation of the actin cytoskeleton controlling spine morphogenesis during development and plasticity.


Blotting; Western; Carrier proteins; Cells; Cultured; Cellular signal transduction; Dendrites; Dendrites/drug effects; Dendrites/ultrastructure; Fixation (Histology); G proteins; Guanine Nucleotide Exchange Factors/physiology; Hippocampus (Brain); Hippocampus/cytology; Hippocampus/embryology; Humans; Indicators and Reagents; Men; Morphogenesis; Neuroplasticity; Neuronal Plasticity/physiology; Phosphorylation; Receptors; Eph Family/physiology; Rho Guanine Nucleotide Exchange Factors; Signal Transduction/physiology; Synapses; Synapses/physiology; Synapses/ultrastructure; Tissue Fixation; Transfection; Western immunoblotting; Women; rac1 GTP-Binding Protein/physiology


Life Sciences | Medical Sciences | Neurosciences

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